title: Serotonin transporter-blocking properties of nefazodone assessed by measurement of platelet serotonin.
abstract: This study aims to determine whether the newly introduced serotonin type 2 (5-HT2) antagonist nefazodone has serotonin (5-HT) transporter-blocking properties at clinical doses in depressed patients. Change in platelet 5-HT was used as an index of the cumulative peripheral 5-HT uptake blockade produced by nefazodone and selective serotonin reuptake inhibitors (SSRIs). Platelet 5-HT was measured before and during treatment with nefazodone (N = 6) or an SSRI (N = 10) in patients with major depression. Corresponding Hamilton Rating Scale for Depression (HAM-D) scores were also obtained over the course of the study. The results of the study demonstrated that the decrease from mean baseline platelet 5-HT after SSRI treatment was significantly greater than the change after nefazodone treatment (-88% vs. -3%; Mann-Whitney U-test, p = 0.0002). Pretreatment platelet 5-HT level, posttreatment platelet 5-HT level, nor the percent decrease in platelet 5-HT correlated with the percent change in HAM-D scores in either treatment group. In conclusion, therapeutic doses of nefazodone do not cause sustained 5-HT uptake inhibition at the platelet 5-HT transporter.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06504, USA.
authors.forename: M
authors.initials: M
authors.lastname: Narayan
authors.forename: G
authors.initials: G
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Cellar
authors.forename: R T
authors.initials: RT
authors.lastname: Mallison
authors.forename: L H
authors.initials: LH
authors.lastname: Price
authors.forename: J C
authors.initials: JC
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010879:Piperazines; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C493230:SLC6A4 protein, human; C051752:nefazodone